Folding pathway of the B1 domain of protein G explored by multiscale modeling
Folding pathway of the B1 domain of protein G explored by multiscale modeling
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DOI：
10.1529/biophysj.107.116095
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发表时间：
2008-02-01
影响因子：
3.4
通讯作者：
Kolinski, Andrzej
中科院分区：
文献类型：
--
作者：
Kmiecik, Sebastian;Kolinski, Andrzej
了解单域蛋白的折叠机制是理解蛋白质折叠的重要一步。近年来，我们建立了一种介观CA-CB侧链蛋白质模型，该模型已成功地应用于蛋白质结构预测、蛋白质热力学研究和蛋白质复合物的建模。在本研究中，该模型被用于一个简单的球形蛋白，igg结合蛋白G （GB1）的B1结构域的折叠过程的详细表征。关于这种蛋白质有大量的实验事实和理论发现。通过无偏从头算模拟，我们证明了GB1的折叠是通过形成一个扩展的折叠核进行的，然后是缓慢的结构微调。值得注意的是，原生交互的子集从一开始就驱动了折叠。新兴的GB1折叠的综合图景完美地匹配和扩展了先前的实验和理论研究。
The understanding of the folding mechanisms of single-domain proteins is an essential step in the understanding of protein folding in general. Recently, we developed a mesoscopic CA-CB side-chain protein model, which was successfully applied in protein structure prediction, studies of protein thermodynamics, and modeling of protein complexes. In this research, this model is employed in a detailed characterization of the folding process of a simple globular protein, the B1 domain of IgG-binding protein G (GB1). There is a vast body of experimental facts and theoretical findings for this protein. Performing unbiased, ab initio simulations, we demonstrated that the GB1 folding proceeds via the formation of an extended folding nucleus, followed by slow structure fine-tuning. Remarkably, a subset of native interactions drives the folding from the very beginning. The emerging comprehensive picture of GB1 folding perfectly matches and extends the previous experimental and theoretical studies.